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H₂S-releasing amphiphilic dipeptide hydrogels are potent S. aureus biofilm disruptors.

ABSTRACT: As a gasotransmitter, hydrogen sulfide (H₂S) has been studied to treat wounds and inflammation, but its potential antimicrobial effects in this context have not been evaluated. An H₂S-releasing dipeptide hydrogel (S-FE), and several non-H₂S-releasing control dipeptides, (C-FE, C-GE, FBA-FE, and FE where S = S-aroylthiooxime, an H₂S donor; C = control, an oxime incapable of H₂S release; FBA = 4-formylbenzamide, also incapable of H₂S release; and E, F, G = glutamic acid, phenylalanine, and glycine, respectively), were studied to correlate differences in their chemical structures and H₂S-releasing abilities with their antimicrobial effects on Staphylococcus aureus bacteria. Dipeptides with Phe (S-FE, C-FE, and FE) self-assembled into nanoribbons in water and displayed β-sheet formation and enhanced fluorescence, while the other two dipeptides (FBA-FE and C-GE) did not form assemblies in water. In vitro experiments with Staphylococcus aureus, which is a commonly found bacterium associated with wounds, showed significant antimicrobial effects from some of the dipeptides. Dipeptide S-FE inhibited bacterial growth more effectively than any of the controls, thereby limiting biofilm formation or disrupting established biofilms. These antimicrobial H₂S-releasing dipeptide hydrogels provide a promising new approach to treat wound infections.

SUBMITTER: Qian Y

PROVIDER: S-EPMC7250531 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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H2S-releasing amphiphilic dipeptide hydrogels are potent S. aureus biofilm disruptors.

Qian Yun Y Altamimi Afnan A Yates Shaina Alston SA Sarkar Santu S Cochran Matthew M Zhou Mingjun M Levi-Polyachenko Nicole N Matson John B JB

Biomaterials science 20200331 9

As a gasotransmitter, hydrogen sulfide (H2S) has been studied to treat wounds and inflammation, but its potential antimicrobial effects in this context have not been evaluated. An H2S-releasing dipeptide hydrogel (S-FE), and several non-H2S-releasing control dipeptides, (C-FE, C-GE, FBA-FE, and FE where S = S-aroylthiooxime, an H2S donor; C = control, an oxime incapable of H2S release; FBA = 4-formylbenzamide, also incapable of H2 ...[more]

PMID: 32232239

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Project description:BackgroundBiofilm formation is an essential virulence factor that creates a highly protected growth mode for Staphylococcus aureus (S. aureus) to survive in any hostile environment. Antibiotic sub-minimal inhibitory concentration (sub-MIC) may modulate the biofilm formation ability of bacterial pathogens, thereby affecting bacterial pathogenesis and infection outcomes. Intense antimicrobial therapy to treat biofilm-associated infections can control the pathogenic infection aggravation but cannot guarantee its complete eradication.ObjectiveThis study aimed to assess the sub-MICs effect of 5 different antimicrobial classes on biofilm-forming capacity among Staphylococcus aureus clinical isolates using three different biofilm quantitation techniques.MethodsIn this study, the effects of 5 different antimicrobial agents, namely, azithromycin, gentamicin, ciprofloxacin, doxycycline, and imipenem, at sub-MICs of 12.5%, 25%, and 50% were tested on 5 different clinical isolates of S. aureus. The biofilms formed in the absence and presence of different antimicrobial sub-MICs were then assessed using the following three different techniques: the crystal violet (CV) staining method, the quantitative PCR (qPCR) method, and the spread plate method (SPM).ResultsBiofilm formation was significantly induced in 64% of the tested conditions using the CV technique. On the other hand, the qPCR quantifying the total bacterial count and the SPM quantifying the viable bacterial count showed significant induction only in 24% and 17.3%, respectively (Fig. 1). The difference between CV and the other techniques indicates an increase in biofilm biomass without an increase in bacterial growth. As expected, sub-MICs did not reduce the viable cell count, as shown by the SPM. The CV staining method revealed that sub-MICs of imipenem and ciprofloxacin had the highest significance rate (80%) showing an inductive effect on the biofilm development. On the other hand, doxycycline, azithromycin, and gentamicin displayed lower significance rates of 73%, 53%, and 47%, respectively.ConclusionExposure to sub-MIC doses of antimicrobial agents induces the biofilm-forming capacity of S. aureus via increasing the total biomass without significantly affecting the bacterial growth of viable count.

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H₂S-releasing amphiphilic dipeptide hydrogels are potent S. aureus biofilm disruptors.

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H<sub>2</sub>S-releasing amphiphilic dipeptide hydrogels are potent S. aureus biofilm disruptors.

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